Impact of intellectual status on response to cognitive task training in patients with schizophrenia.

Cognitive remediation is a promising rehabilitation procedure for people with schizophrenia, but very little is known about who can benefit. In the current analyses, we examined the role of pre-morbid and morbid intellectual function in predicting response to cognitive remediation in a sample of 152 patients diagnosed with schizophrenia or schizoaffective disorder. They were participants in a trial of work therapy and cognitive remediation and had been randomized to receive either Neurocognitive Enhancement Therapy with Work Therapy (NET+WT) or Work Therapy only (WT only). For the current analyses, patients were divided into three intellectual subgroups based on their pattern of premorbid and morbid deficits (preserved intelligence, compromised intelligence, and deteriorated intelligence), and their cognitive remediation outcomes were examined. Cognitive remediation response was measured in two ways: normalization of performance on a computerized training task, and pre-post neuropsychological test performance. Subjects in NET+WT showed greater improvement in cognition than those in WT only, but response differed by intellectual group. For patients in the compromised group, those in NET+WT showed a significantly higher proportion of task normalization than those in the WT only condition, but no such differences were found with the preserved and deteriorated intellectual groups. For patients in the preserved and deteriorated intellectual groups, those in the NET+WT condition showed significantly greater improvement in the analysis of pre-post neuropsychological test performance, but this difference was not found in the compromised intellectual group. These findings suggest that the compromised intellectual group, which had the lowest frequency of normal performers at intake, benefited from NET by achieving dramatic increases in normalization, but that they had difficulty in generalizing these gains to untrained tasks. Those in the preserved and deteriorated intellectual groups were more successful in generalizing their training.

Cognitive training of verbal memory using a dichotic listening paradigm: impact on symptoms and cognition.

OBJECTIVE: The objective was to investigate the impact of a verbal memory training task on psychiatric symptoms and cognition in schizophrenia. METHOD: As part of a larger, 6-month cognitive remediation program, 57 patients with schizophrenia were randomly assigned to receive performance-based, hierarchical training on a verbal memory task based on a dichotic listening (DL) with distracter paradigm. These patients were compared with 68 patients who had been randomly assigned to a control condition. RESULTS: Training on the DL task was not associated with changes in general psychopathology or auditory hallucinations (AH) specifically. Training was associated with improvements in verbal memory, but not attention. CONCLUSION: The current investigation adds to the growing literature on the effectiveness of cognitive remediation training and indicates that training on the DL task enhances verbal episodic memory. The results do not support the use of DL training as a method for reducing AH.

Detection of the CD56+/CD45- immunophenotype by flow cytometry in neuroendocrine malignancies.

AIMS: Antibodies against CD56 are primarily used in flow cytometric studies to detect natural killer cells. However, they may be useful in the identification of neuroendocrine malignancies, especially if the cells do not express CD45, indicating a non-leucocyte origin. METHODS: A retrospective review was conducted on all solid tissue flow cytometric studies performed between January 1997 and September 2001, to identify all cases with a CD56+/CD45- immunophenotype. RESULTS: Twelve neuroendocrine malignancies (five metastatic small cell carcinomas, three Merkel cell carcinomas, two metastatic undifferentiated neuroendocrine carcinomas, one metastatic pancreatic neuroendocrine carcinoma, and one neuroblastoma) were identified. CONCLUSIONS: CD56+/CD45- neuroendocrine malignancies are only rarely detected in the flow cytometric analysis of solid tissue samples. However, the recognition of this immunophenotype is important to avoid their misclassification as natural killer cell malignancies. Furthermore, flow cytometry assists in the rapid identification of such cases, so that appropriate immunohistochemical studies can be performed to facilitate their correct diagnosis.

Emotional discomfort and impairments in verbal memory in schizophrenia.

Research has demonstrated that impairments in verbal memory in schizophrenia are linked with psychosocial deficits. Less is known, however, about their relationship to clinical features of illness. This study explores the hypothesis that impairments in verbal memory, particularly forms of memory requiring deeper levels of encoding, are uniquely linked to symptoms of dysphoria or emotional discomfort. Accordingly, we examined the association between concurrent measures of symptoms and verbal memory for 84 subjects with schizophrenia. Measures of positive, negative, cognitive, excitement and emotional discomfort symptoms were derived from factor scores of the Positive and Negative Syndrome Scale. Verbal memory was assessed using two tests requiring relatively superficial levels of encoding: The Hopkins Verbal Memory Test and the Digit Span subtest; and one test requiring deeper levels of encoding: the Logical Memory subtests I and II. As predicted, multiple regressions controlling for age, education and attention revealed that poorer performance on Logical Memory was strongly associated with greater levels of emotional discomfort (R(2)=0.22 and 0.25, respectively) while performance on the Hopkins test was related to cognitive symptoms scores (R(2)=0.08 and 0.09, respectively). Implications for the conceptualization of verbal memory deficits in schizophrenia are discussed.

Personality and psychopathology in schizophrenia: the association between personality traits and symptoms.

Research has indicated that stable individual differences in personality exist among persons with schizophrenia, and that they likely predate the onset of illness. Little is known, however, about whether individual differences in personality are related to levels of psychopathology. This study tested the hypotheses that levels of Extroversion, Neuroticism, and Psychoticism are associated with symptomatology. Accordingly, measures of these dimensions of personality and of symptomatology were obtained simultaneously for 113 male subjects with schizophrenia or schizoaffective disorder. Next, subjects were characterized as having high or low levels on each personality dimension and their scores on the five components of the Positive Negative Syndrome Scale were compared using multivariate and univariate procedures. Results indicate that extroverted subjects had lower levels of Positive, Negative, and Emotional Discomfort symptoms, and higher levels of Excitement symptoms than introverted subjects. Subjects with higher levels of Neuroticism had higher levels of Positive and Emotional Discomfort symptoms than subjects with lower levels of Neuroticism. No differences in symptoms were found among subjects with higher versus lower levels of Psychoticism. Results suggest individual differences in personality are associated with psychopathology in schizophrenia and may help further explain the heterogeneity widely observed in this disorder.

Insight and interpersonal function in schizophrenia.

Research has linked impaired insight in schizophrenia to poorer medication compliance and treatment outcome. It is unclear, however, whether poorer interpersonal function is also associated with impaired insight. To examine this question, subjects with schizophrenia or schizoaffective disorder were classified as having unimpaired (N = 44) or impaired (N = 57) insight, and their scores on Heinrichs et al.'s Quality of Life (QOL) Scale were compared. Multiple regressions were conducted to determine the relationship between individual components and social function. Results indicate that subjects with impaired insight had significantly poorer QOL interpersonal relation and intrapsychic foundation scores than unimpaired subjects, despite having equivalent deficit symptoms. Unawareness of the social consequences of illness was found to be the component of insight more closely linked to social dysfunction. This suggests that impairments in insight may be uniquely associated with social dysfunction.

A WT1 antisense oligonucleotide inhibits proliferation and induces apoptosis in myeloid leukaemia cell lines.

The response of the CML-BC cell line, K562, the myelomonocytic cell line MM6 and the promyelocytic leukaemia cell line HL-60, to a 15 mer WT1 antisense oligonucleotide, targeted to the translation initiation site of the WT1 mRNA was examined. K562 cells exposed to 0.4 microM antisense oligonucleotide showed markedly reduced proliferation which was associated with reduced cell viability. Sense, scrambled and mutant antisense oligonucleotides had no effect on the proliferation of K562 cells. MM6 cells exposed to 0.4 microM antisense oligonucleotide also showed significantly reduced cellular proliferation which was also accompanied by loss of cell viability. In the K562 and MM6 antisense cultures that exhibited reduced cell viability, both DNA fragmentation and morphological features consistent with apoptosis could be identified. In contrast the growth of HL-60 cells was unaffected by exposure to 0.4 microM antisense oligonucleotide. In each of the cell lines examined, WT1 antisense oligonucleotide abrogated WT1 protein expression, and analysis of WT1 coding sequence in these cells showed that no oncogenic point mutations in the gene were present. We propose therefore that in some myeloid leukaemia cell lines, the expression of a normal WT1 protein is necessary for cell proliferation and that it plays a role in maintaining the viability of some leukaemia cells.

Neuropsychological prognosis and clinical recovery.

This report examines prognostic implications of neuropsychological deficit for clinical symptomatic improvement. Neuropsychological performance levels are related to the Brief Psychiatric Rating Scale thinking disturbance, paranoid disturbance, withdrawal/retardation, and anxiety/depression scales at hospital admission and discharge in 68 schizophrenic and psychotic and nonpsychotic mood disorder patients. Findings indicate a relationship between neurocognitive deficit and thinking disturbance at admission; however, neuropsychological impairment predicts blunted affect/emotional withdrawal at discharge, after the acute psychopathology resolves. Neuropsychological deficit is nonspecific, occurring across a broad range of cognitive-perceptual functions. These data suggest that neuropsychological dysfunction may be prognostic of a more chronic residual disorder in both schizophrenia and major psychotic and nonpsychotic mood disorder syndromes.

A flow cytometric study of cell death: failure of some models to correlate with morphological assessment.

The balance between cell death and cell proliferation is a significant factor in the growth kinetics of normal and neoplastic tissues. Distinction between the two major forms of cell death, necrosis and apoptosis, is now recognized as important in understanding mechanisms regulating cell survival. A recent approach in the study of apoptosis has been the use of flow cytometry, with some reports indicating that, when stained with propidium iodide (PI), the DNA of apoptotic cells has decreased fluorescence compared with that of viable cells. In this study, we investigated a flow cytometric procedure which used the simultaneous analysis of DNA content and 90 degrees light scatter (90LS). Significant differences in the PI staining pattern and a shift in 90LS were observed when apoptotic death occurred at different stages of the cell cycle. Importantly, such differences only allowed accurate quantification of apoptosis when it occurred in G1. While necrosis could be distinguished from apoptosis when examined during its early stages, a similar staining pattern to that found with apoptosis was observed when necrosis was examined during its latter stages. The results indicate that the measurement of DNA staining cannot be exclusively relied upon to detect apoptosis occurring in all models. However it is useful in the investigation of this process when the death occurs in G1, in that the method offers a rapid means for quantification.

Differential rate of neuropsychological dysfunction in psychiatric disorders: comparison between the Halstead-Reitan and Luria-Nebraska batteries.

This report examined the rate of agreement between scores of the Halstead-Reitan and Luria-Nebraska Neuropsychological Batteries in the classification of impaired and nonimpaired performance of 55 schizophrenic and 64 affective disorder patients: 65.2% for schizophrenics and 67.5% for those with affective disorder, with greater impairment on the Halstead-Reitan battery.

Evaluation of semiautomated procedure for lymphocyte subset analysis.

The findings of recent surveys indicate a need for standardisation in lymphocyte subset analysis by flow cytometry. Major areas of concern are the methods used for labelling subsets and the choice of appropriate monoclonal antibodies. A standard dual colour manual whole blood lysis technique for flow cytometry was compared with the recently available Coulter Q-Prep EPICS technique. Overall, there was no significant difference (Student's t test) between the use of anticoagulated blood treated with heparin or EDTA. When normal subjects were examined there was a decrease in the absolute number of CD3+ and Leu-7+/CD8- cells and an increase in CD19+ and CD20+ cells. When human immunodeficiency virus (HIV) antibody positive subjects were examined there was a significant decrease in the absolute number of CD2+, CD3+, CD4+ and Leu 7+/CD8- cells and an absolute increase in CD19+ and CD20+ cells. CD8+ cells were decreased only with the Cyto-Stat reagents. Occasionally, the Q-Prep did not lyse the red cells efficiently. While the Q-Prep EPICS system has the potential to standardise and automate the labelling procedures used in lymphocyte subset analysis, further refinement, such as the choice of monoclonal antibodies or alternative preparative reagents, may be required to resolve the cause of the discordant findings between the two approaches.

The proportion of suppressor-inducer T-lymphocytes is reduced in recurrent aphthous stomatitis.

A flow cytometric analysis of peripheral blood lymphocytes was undertaken in recurrent aphthous stomatitis patients. The project aimed at detecting differences within lymphocyte subsets using type-specific monoclonal antibodies. Peripheral blood samples were taken from RAS patients in both active and remission phases of the disease and from a group of healthy control subjects. There were no statistical differences between the active and remission phases within any of the lymphocyte subsets examined. There was, however, a significant difference between the RAS group and the control group. RAS patients have depressed CD4+ cell numbers and elevated CD8+ cell numbers. The CD4:CD8 ratio is also depressed. A dissection of the CD4+ subset shows raised numbers of CD4+, 4B4+ lymphocytes and depressed numbers of CD4+, 2H4+ lymphocytes. Previous studies have shown disruption of peripheral blood lymphocyte numbers in Behçet's syndrome. A similar pattern has now been shown in uncomplicated cases of minor RAS.